Nab-Paclitaxel + Paclitaxel + Ramucirumab for Stomach Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must not be taking: Antibiotics

Disqualifiers: Brain metastases, Intolerance to taxanes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 24 weeks

30 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it does mention that treatment with therapeutic oral or IV antibiotics within 14 days prior to the start of the trial is not allowed, unless they are prophylactic (preventive) antibiotics and signs of active infection have resolved.

What data supports the effectiveness of the drug Nab-Paclitaxel + Paclitaxel + Ramucirumab for stomach cancer?

Research shows that nab-paclitaxel, a form of paclitaxel, is effective and safe for treating advanced gastric cancer when combined with ramucirumab. Additionally, nab-paclitaxel has been used successfully in other cancers like breast and lung cancer, suggesting its potential effectiveness in stomach cancer. ^{1 2 3 4 5}

Is the combination of Nab-Paclitaxel, Paclitaxel, and Ramucirumab safe for humans?

Nab-Paclitaxel (also known as Abraxane) has been studied for safety in various cancers, including gastric cancer, lung cancer, and melanoma. It is designed to improve tolerability compared to traditional formulations, and studies suggest it is generally safe for human use, though specific side effects can vary depending on the condition being treated. ^{1 2 3 4 6}

How is the drug combination of Nab-Paclitaxel, Paclitaxel, and Ramucirumab unique for treating stomach cancer?

This drug combination is unique because Nab-Paclitaxel is a solvent-free form of Paclitaxel that improves solubility and reduces side effects, making it more convenient and potentially safer than traditional Paclitaxel. It is combined with Ramucirumab, which is already a standard treatment, to enhance effectiveness in treating advanced gastric cancer. ^{1 5 7 8 9}

What is the purpose of this trial?

This phase I trial tests the safety, side effects and best dose of nab-paclitaxel pressurized intraperitoneal aerosolized chemotherapy (PIPAC) in combination with second-line chemotherapy, paclitaxel and ramucirumab, and tests how well they work in treating stomach cancer that has spread from where it first started to the tissue that lines the abdominal wall and organs (peritoneal metastases). Paclitaxel is in a class of medications called antimicrotubule agents. It stops tumor cells from growing and dividing and may kill them. Nab-paclitaxel is an albumin-stabilized nanoparticle formulation of paclitaxel which may have fewer side effects and work better than other forms of paclitaxel. PIPAC delivers chemotherapy, such as nab-paclitaxel, that has been turned into a fine mist (aerosolized) at a high pressure directly into the abdominal cavity. Aerosolized chemotherapy delivered directly into the peritoneal space has been shown to deliver higher drug concentrations to the tumor. Ramucirumab is a monoclonal antibody that may prevent the growth of new blood vessels that tumors need to grow. Giving nab-paclitaxel PIPAC in combination with paclitaxel and ramucirumab may be safe, tolerable, and/or effective in treating gastric cancer patients with peritoneal metastases.

Research Team

Yanghee Woo

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for stomach cancer patients with peritoneal metastases, who are ready to try a combination of treatments. Participants should be suitable for second-line chemotherapy and have not had prior PIPAC or allergic reactions to the drugs used in this study.

Inclusion Criteria

My urine protein levels are low or normal.

I've had a full medical check-up in the last 28 days.

Platelets ≥ 100,000/mcL (within 28 days prior to day 1 of protocol therapy)

Exclusion Criteria

I cannot tolerate taxane medications.

I am not pregnant or breastfeeding.

Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive nab-paclitaxel PIPAC intraperitoneally and standard of care paclitaxel and ramucirumab intravenously. Cycles repeat every 8 weeks for up to 3 cycles.

24 weeks

Multiple visits for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up includes regular assessments every 3 months for the first year, then every 6 months.

Up to 2 years

Regular visits every 3 to 6 months

Treatment Details

Interventions

• Nab-paclitaxel
• Paclitaxel
• Ramucirumab

Trial Overview The trial tests nab-paclitaxel PIPAC's safety and optimal dose when combined with paclitaxel and ramucirumab. It evaluates how well these treatments work against stomach cancer that has spread to the abdominal lining.

Participant Groups

Group I: Treatment (nab-paclitaxel PIPAC, paclitaxel, ramucirumab) Experimental Treatment 9 Interventions

Patients receive nab-paclitaxel PIPAC IP over 40 minutes on day 1 and SOC paclitaxel IV over 60 minutes on days 15, 22, 29, 43, and 50 and ramucirumab IV over 30-60 minutes on days 15, 29 and 43 of each cycle. Cycles repeat every 8 weeks (56 days) for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients may then continue SOC paclitaxel IV on days 1, 8, and 15 and ramucirumab IV on days 1 and 15 of each cycle per physician as deemed appropriate. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, tumor biopsy, and CT or MRI throughout the study.

Nab-paclitaxel is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Abraxane for:

• Metastatic breast cancer
• Non-small cell lung cancer
• Adenocarcinoma of the pancreas

Approved in European Union as Abraxane for:

• Metastatic breast cancer
• Non-small cell lung cancer
• Adenocarcinoma of the pancreas

Approved in Canada as Abraxane for:

• Metastatic breast cancer
• Non-small cell lung cancer
• Adenocarcinoma of the pancreas

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a phase II trial involving 45 patients with advanced gastric cancer, the combination of nab-paclitaxel and ramucirumab achieved an overall response rate of 54.8%, indicating significant efficacy as a second-line treatment.

The treatment was associated with manageable side effects, primarily decreased neutrophil and white blood cell counts, but no treatment-related deaths occurred, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of nab-paclitaxel in combination with ramucirumab in patients with previously treated advanced gastric cancer. Bando, H., Shimodaira, H., Fujitani, K., et al.[2023]

In a study involving 17 patients with malignant solid tumors, nab-paclitaxel (Abraxane) showed a significantly higher exposure to unbound paclitaxel compared to solvent-based paclitaxel, which may enhance its effectiveness against tumors.

The pharmacokinetics of nab-paclitaxel remained consistent across treatment cycles, indicating stable drug behavior and suggesting improved tolerability and efficacy due to its unique formulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized crossover pharmacokinetic study of solvent-based paclitaxel and nab-paclitaxel. Gardner, ER., Dahut, WL., Scripture, CD., et al.[2022]

In a phase II study involving 43 patients with non-small-cell lung cancer, Abraxane (260 mg/m2) demonstrated a 16% overall response rate and a 49% disease control rate, indicating its efficacy as a first-line therapy.

Abraxane was well tolerated, with no severe hypersensitivity reactions reported and only 5% of patients discontinuing treatment due to mild toxicities, suggesting a favorable safety profile for this novel formulation of paclitaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abraxane, a novel Cremophor-free, albumin-bound particle form of paclitaxel for the treatment of advanced non-small-cell lung cancer. Green, MR., Manikhas, GM., Orlov, S., et al.[2022]

In a study involving 74 patients with metastatic melanoma, nab-Paclitaxel showed a response rate of 21.6% in chemotherapy-naive patients and 2.7% in previously treated patients, indicating better efficacy in those who had not undergone prior treatment.

The treatment was well tolerated, with 78% of previously treated patients and 49% of chemotherapy-naive patients able to complete therapy without dose reductions, suggesting a favorable safety profile compared to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2 clinical trial of nab-paclitaxel in previously treated and chemotherapy-naive patients with metastatic melanoma. Hersh, EM., O'Day, SJ., Ribas, A., et al.[2020]

Nab-paclitaxel, a new formulation of paclitaxel, has shown a good safety and efficacy profile for treating metastatic breast cancer (MBC), although there is limited data on its impact on overall survival.

In combination with gemcitabine, nab-paclitaxel significantly improves survival in advanced pancreatic cancer (PC) and demonstrates better results in non-small-cell lung cancer (NSCLC) patients with squamous histology, highlighting its potential as a valuable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy evaluation of albumin-bound paclitaxel. Cecco, S., Aliberti, M., Baldo, P., et al.[2015]

Nab-paclitaxel was well tolerated in pediatric solid tumor models, with a maximum weight loss of about 10% that returned to baseline after treatment, indicating a favorable safety profile.

The treatment showed significant efficacy, improving event-free survival in 19 out of 20 solid tumor xenograft models, particularly demonstrating high activity against Ewing sarcoma and rhabdomyosarcoma, making it a promising candidate for further pediatric evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial testing (stage 1) of the tubulin binding agent nanoparticle albumin-bound (nab) paclitaxel (Abraxane(®)) by the Pediatric Preclinical Testing Program (PPTP). Houghton, PJ., Kurmasheva, RT., Kolb, EA., et al.[2022]

Nab-paclitaxel, a nanoparticle albumin-bound form of paclitaxel, is the first nanotechnology-based drug approved for cancer treatment, showing significant promise in breast and pancreatic cancers.

This innovative drug not only enhances the effectiveness and reduces the toxicity of traditional treatments but also demonstrates activity in cancers that typically do not respond to standard taxane therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nanoparticle albumin bound Paclitaxel in the treatment of human cancer: nanodelivery reaches prime-time? Cucinotto, I., Fiorillo, L., Gualtieri, S., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

A phase II study of nab-paclitaxel in combination with ramucirumab in patients with previously treated advanced gastric cancer. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Randomized crossover pharmacokinetic study of solvent-based paclitaxel and nab-paclitaxel. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Abraxane, a novel Cremophor-free, albumin-bound particle form of paclitaxel for the treatment of advanced non-small-cell lung cancer. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

A phase 2 clinical trial of nab-paclitaxel in previously treated and chemotherapy-naive patients with metastatic melanoma. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy evaluation of albumin-bound paclitaxel. [2015]

6. United States pubmed.ncbi.nlm.nih.gov

Initial testing (stage 1) of the tubulin binding agent nanoparticle albumin-bound (nab) paclitaxel (Abraxane(®)) by the Pediatric Preclinical Testing Program (PPTP). [2022]

7. Japan pubmed.ncbi.nlm.nih.gov

Nanoparticle albumin-bound paclitaxel and ramucirumab versus paclitaxel and ramucirumab as second-line chemotherapy for unresectable advanced or recurrent gastric cancer: a multicenter, propensity score-matched analysis (CROSS SELL study). [2023]

8. China pubmed.ncbi.nlm.nih.gov

A small-scale, exploratory real-world study of nab-paclitaxel combined with oxaliplatin and tegafur in the perioperative treatment of advanced gastric cancer: a study protocol for a real-world clinical trial. [2023]

9. Egypt pubmed.ncbi.nlm.nih.gov

Nanoparticle albumin bound Paclitaxel in the treatment of human cancer: nanodelivery reaches prime-time? [2022]